Schiffer, Jodie et al. (2017) International Worm Meeting "How do worms determine their readiness to cope with environmental stress?"

Stumbur, Stephanie, Heath, William, Tam, Hannah, McGowan, Natalie, Vogelaar, Abigail, Schiffer, Jodie, Apfeld, Javier, Stanley, Julian

[International Worm Meeting, 2017]

At any time in their life, worms may encounter harmful environmental conditions such as high concentrations of oxidants or high temperature. We are interested in understanding how worms prepare for these potentially lethal events. We want to know: what establishes how prepared they are? To determine the mechanisms that control survival under harmful conditions, we are examining the effects of strong loss-of-function and null mutants in a collection of intercellular signaling receptors and transcription factors regulated by these receptors. We measure survival under oxidative stress and at high temperature using a "Lifespan Machine" cluster of flat-bed scanners [1]. This automated technology presents substantial advancements in throughput and sensitivity compared to manual methods. Using this approach, we have identified several signaling receptors and transcription factors that regulate survival under oxidative conditions. Interestingly, we identified both receptors and transcription factors that function to either confer or limit oxidative-stress resistance. This indicates that the combined level of activity of these genes sets the worm's readiness to cope with oxidative stress. We are currently investigating whether these genes act together or independently to determine the worm's normal level of resistance to various stressors, and the mechanisms that establish the normal activity levels of each of these genetic determinants of stress resistance. Reference: 1. Stroustrup N, Ulmschneider BE, Nash ZM, Lopez-Moyado IF, Apfeld J, Fontana W. The Caenorhabditis elegans Lifespan Machine. Nature Methods. 2013;10(7):665-70.

Schiffer, Jodie et al. (2021) International Worm Meeting "Caenorhabditis elegans processes sensory information to choose between freeloading and self-defense strategies"

McGowan, Natalie, Tam, Hannah, Stroustrup, Nicholas, Amrit, Francis Raj Ghandi, Heath, William, Stanley, Julian, Vogelaar, Abigail, Schiffer, Jodie, Servello, Francesco, Martin, Olivier, Xu, Yuyan, Stumbur, Stephanie, Apfeld, Javier, Eder, Matthias, Johnsen, Sean, Serkin, William, Brennan, Sarah, Ghazi, Arjumand

[International Worm Meeting, 2021]

Hydrogen peroxide is the preeminent chemical weapon that organisms use for combat. Individual cells rely on conserved defenses to prevent and repair peroxide-induced damage, but whether similar defenses might be coordinated across cells and tissues in animals remains poorly understood. Here, we screen a collection of sensory neuron genetic ablations in the nematode C. elegans to determine their effects on resistance to peroxide. We identify a neuronal circuit that processes information perceived by two of those sensory neurons to control the induction of hydrogen peroxide defenses in the organism. In the presence of E. coli, C. elegans'food source, the animal's neurons signal via TGFb-insulin/IGF1 relay to target tissues to repress expression of catalases and other hydrogen peroxide defenses. We found that catalases produced by E. coli can compensate for the animal's downregulation of catalases by depleting hydrogen peroxide from the local environment and thereby protecting C. elegans. This adaptive strategy is the first example of a multicellular organism modulating its defenses when it expects to freeload from the protection provided by molecularly orthologous defenses from another species.

Stumbur, Stephanie et al. (2021) International Worm Meeting "C. elegans regulates its behavior via serotonergic signaling to find food and hydrogen peroxide protection."

McGowan, Natalie, Serkin, William, Sevedolmohadesin, Maedeh, Venkatachalam, Vivek, Stumbur, Stephanie, Apfeld, Javier, Schiffer, Jodie

[International Worm Meeting, 2021]

Hydrogen peroxide is a pervasive chemical weapon used by many species to damage their prey or to protect themselves from their pathogens. Cells rely on conserved defense mechanisms, including catalases, to avoid the damage that hydrogen peroxide inflicts on their macromolecules We recently discovered that C. elegans represses those defenses in response to sensory perception of E. coli, the nematode's food source in the lab, because E. coli can deplete hydrogen peroxide from the local environment and thereby protect the nematodes1. Here, we investigated the extent to which C. elegans can tell the difference between bacteria that provide hydrogen peroxide protection and bacteria that do not. To address that question, we determined the extent to which hydrogen peroxide modulates the behavior of C. elegans in food lawns of wildtype E. coli and mutant E. coli unable to degrade hydrogen peroxide. In the absence of hydrogen peroxide in the environment, C. elegans did not exhibit a preference between these two bacteria stains. However, in the presence of hydrogen peroxide, C. elegans remained on the wildtype bacteria lawn but was much more likely to leave the lawn of the bacteria that do not degrade hydrogen peroxide. This nematode behavior was conserved when we used catalase-positive and catalase-negative bacterial strains from the natural C. elegans microbiome, suggesting that this decision-making occurs in the natural environment. To determine how C. elegans senses and responds to bacteria and environmental hydrogen peroxide, we measured calcium dynamics in ciliated sensory neurons. We identified several neuronal classes that respond to hydrogen peroxide in a bacteria-dependent manner. In addition, genetic analysis showed that serotonin signaling regulates this nematode behavior. Our findings demonstrate that the cross-kingdom interactions between C. elegans and bacteria in their microbiome determine the nematode food-leaving behavior via serotonergic signaling, enabling nematode populations to find safety from hydrogen peroxide. 1. Schiffer JA et al. (2020). Caenorhabditis elegans processes sensory information to choose between freeloading and self-defense strategies. eLife.